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Breast cancer immunotherapy

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https://www.readbyqxmd.com/read/29456568/harnessing-the-immune-system-in-the-battle-against-breast-cancer
#1
REVIEW
Elizabeth S Nakasone, Sara A Hurvitz, Kelly E McCann
Breast cancer is the most prevalent malignancy in women and the second most common cause of cancer-related death worldwide. Despite major innovations in early detection and advanced therapeutics, up to 30% of women with node-negative breast cancer and 70% of women with node-positive breast cancer will develop recurrence. The recognition that breast tumors are infiltrated by a complex array of immune cells that influence their development, progression, and metastasis, as well as their responsiveness to systemic therapies has sparked major interest in the development of immunotherapies...
2018: Drugs in Context
https://www.readbyqxmd.com/read/29456158/autologous-ipsc-based-vaccines-elicit-anti-tumor-responses-in-vivo
#2
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
February 8, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29449898/targeted-therapy-of-brain-metastases-latest-evidence-and-clinical-implications
#3
REVIEW
Rodica Di Lorenzo, Manmeet S Ahluwalia
Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29445216/evaluation-of-her2-specific-peptide-ligand-for-its-employment-as-radiolabeled-imaging-probe
#4
Hadis Honarvar, Enrica Calce, Nunzianna Doti, Emma Langella, Anna Orlova, Jos Buijs, Valentina D'Amato, Roberto Bianco, Michele Saviano, Vladimir Tolmachev, Stefania De Luca
HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29438689/glycans-pave-the-way-for-immunotherapy-in-triple-negative-breast-cancer
#5
Mariana Salatino, María Romina Girotti, Gabriel A Rabinovich
The clinical efficacy of therapies targeting the PD-1/PD-L1 pathway is still limited. In this issue of Cancer Cell, Li and colleagues identify a PD-L1 glycosylation-based mechanism in triple-negative breast cancer that fosters immunosuppression by enhancing interactions with PD-1. Targeting glycosylated PD-L1 with a drug-conjugated antibody opens new avenues for treatment.
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29434859/silencing-of-suppressor-of-cytokine-signaling-1-enhances-the-immunological-effect-of-mucin-1-calreticulin-primed-4t1-cell-treated-dendritic-cells-in-breast-cancer-treatment
#6
Song Qin, Zhipeng Gao, Yu Liu, Changbai Liu, Jun Wang, Li Li Zou
In cancer immunotherapy, dendritic cell (DC)-based vaccines represent a promising, yet challenging, treatment method. In addition to overcoming the low expression levels of antigenic epitopes on cancer cells, it is also necessary to overcome the inhibitory effect of suppressor of cytokine signaling 1 (SOCS1) on DC self-antigen presentation. Our group previously demonstrated that calreticulin (CRT) translocated type I transmembrane glycoprotein mucin 1 (MUC1), a breast cancer antigen, to the surface of 4T1 cells, and that treatment with MUC1-CRT-primed 4T1 cell-treated DCs induced apoptosis in a breast cancer cell line...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29428415/genome-scale-signatures-of-gene-interaction-from-compound-screens-predict-clinical-efficacy-of-targeted-cancer-therapies
#7
Peng Jiang, Winston Lee, Xujuan Li, Carl Johnson, Jun S Liu, Myles Brown, Jon Christopher Aster, X Shirley Liu
Identifying reliable drug response biomarkers is a significant challenge in cancer research. We present computational analysis of resistance (CARE), a computational method focused on targeted therapies, to infer genome-wide transcriptomic signatures of drug efficacy from cell line compound screens. CARE outputs genome-scale scores to measure how the drug target gene interacts with other genes to affect the inhibitor efficacy in the compound screens. Such statistical interactions between drug targets and other genes were not considered in previous studies but are critical in identifying predictive biomarkers...
February 6, 2018: Cell Systems
https://www.readbyqxmd.com/read/29427082/identification-of-tumor-reactive-b-cells-and-systemic-igg-in-breast-cancer-based-on-clonal-frequency-in-the-sentinel-lymph-node
#8
Jonathan R McDaniel, Stephanie C Pero, William N Voss, Girja S Shukla, Yujing Sun, Sebastian Schaetzle, Chang-Han Lee, Andrew P Horton, Seth Harlow, Jimmy Gollihar, Jared W Ellefson, Christopher C Krag, Yuri Tanno, Nikoletta Sidiropoulos, George Georgiou, Gregory C Ippolito, David N Krag
A better understanding of antitumor immune responses is the key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Using a synergistic combination of high-throughput B-cell sequencing and quantitative immunoproteomics, we describe the prospective identification of tumor-reactive SN B cells (based on clonal frequency) and also demonstrate an unequivocal link between affinity-matured expanded B-cell clones in the SN and antitumor IgG in the blood...
February 9, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29424936/checkpoint-inhibitors-in-triple-negative-breast-cancer-tnbc-where-to-go-from-here
#9
REVIEW
Maryann J Kwa, Sylvia Adams
Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway in maintaining immunosuppression in the tumor microenvironment...
February 9, 2018: Cancer
https://www.readbyqxmd.com/read/29424297/use-of-immunotherapy-to-treat-metastatic-breast-cancer
#10
Andrea Nicolini, Vivian Barak, Piermario Biava, Paola Ferrari, Giuseppe Rossi, Angelo Carpi
This article reviews the principal attempts of immune-modulation or immune therapy in metastatic breast cancer. It considers their rationale and reports on results from the relevant key clinical trials. Immune-modulatory or immune-stimulating cytokines used alone or combined with conventional therapies is among the principal approaches of immune manipulation in breast cancer. As this issue was recently reviewed by us, the aim of the current article is to discuss our updated and unpublished data on this topic...
February 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29424261/the-breast-tumor-microenvironment-role-in-cancer-development-progression-and-response-to-therapy
#11
Suruchi Mittal, Nicola J Brown, Ingunn Holen
Numerous clinical and pre-clinical studies have provided ample evidence supporting that the tumor microenvironment plays a significant role during breast cancer development, progression and in determining the therapeutic response. Areas covered: This review focuses on the evolving concept of the microenvironment as the critical participant in each step of the multi-stage process of malignant progression. Currently, only a small number of molecules form part of routine molecular diagnostics in breast caner, but microenvironment-derived biomarkers are potential additions to existing predictive and prognostic marker panels...
February 9, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29413765/a-comprehensive-immunologic-portrait-of-triple-negative-breast-cancer
#12
Zhixian Liu, Mengyuan Li, Zehang Jiang, Xiaosheng Wang
Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed an exhaustive analysis of immunogenic signatures in TNBC based on 2 large-scale breast cancer (BC) genomic data. We compared enrichment levels of 26 immune cell activities and pathways among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features...
February 4, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29411237/cell-growth-inhibition-and-apoptosis-in-breast-cancer-cells-induced-by-anti-fzd7-scfvs-involvement-of-bioinformatics-based-design-of-novel-epitopes
#13
Neda Zarei, Mehdi Fazeli, Mozafar Mohammadi, Foroogh Nejatollahi
BACKGROUND: FZD7 has a critical role as a surface receptor of Wnt/β-catenin signaling in cancer cells. Suppressing Wnt signaling through blocking FZD7 is shown to decrease cell viability, metastasis and invasion. Bioinformatic methods have been a powerful tool in epitope designing studies. Small size, high affinity and human origin of scFv antibodies have provided unique advantages for these recombinant antibodies. METHODS: Two epitopes from extracellular domain of FZD7 were designed using bioinformatic methods...
February 6, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29399412/a-virus-like-particle-immunotherapy-targeting-epitope-specific-anti-xct-expressed-on-cancer-stem-cell-inhibits-the-progression-of-metastatic-cancer-in-vivo
#14
Elisabetta Bolli, John P O'Rourke, Laura Conti, Stefania Lanzardo, Valeria Rolih, Jayne M Christen, Giuseppina Barutello, Marco Forni, Federica Pericle, Federica Cavallo
Aggressive forms of breast cancer, such as Her2+ and triple negative breast cancer (TNBC), are enriched in breast cancer stem cells (BCSC) and have limited therapeutic options. BCSC represent a key cellular reservoir for relapse, metastatic progression and therapeutic resistance. Their ability to resist common cytotoxic therapies relies on different mechanisms, including improved detoxification. The cystine-glutamate antiporter protein xCT (SLC7A11) regulates cystine intake, conversion to cysteine and subsequent glutathione synthesis, protecting cells against oxidative and chemical insults...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29394917/analysis-of-tumour-infiltrating-lymphocytes-reveals-two-new-biologically-different-subgroups-of-breast-ductal-carcinoma-in-situ
#15
Marie Beguinot, Marie-Melanie Dauplat, Fabrice Kwiatkowski, Guillaume Lebouedec, Lucie Tixier, Christophe Pomel, Frederique Penault-Llorca, Nina Radosevic-Robin
BACKGROUND: Tumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Thus, it has been suggested that TIL density or/and immunophenotype could serve as biomarkers for selection of IBC patients for immunotherapy. However, much less is known about significance of TILs in breast ductal carcinoma in situ (DCIS). METHODS: We retrospectively investigated TIL density and immunophenotype in 96 pure DCIS and 35 microinvasive carcinomas (miCa)...
February 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29391830/neoadjuvant-treatments-in-triple-negative-breast-cancer-patients-where-we-are-now-and-where-we-are-going
#16
REVIEW
Claudia Omarini, Giorgia Guaitoli, Stefania Pipitone, Luca Moscetti, Laura Cortesi, Stefano Cascinu, Federico Piacentini
Triple-negative breast cancer (TNBC) remains the poorest-prognosis breast cancer (BC) subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29388072/pharmacotherapeutic-management-of-breast-cancer-in-elderly-patients-the-promise-of-novel-agents
#17
REVIEW
Catherine Terret, Chiara Russo
As its incidence increases with age, breast cancer in elderly patients takes on a growing importance in clinical oncology practice. Management decisions are challenging because there is a lack of high-quality evidence in this heterogeneous population. Epidemiological studies have shown that breast cancer mortality does not decrease substantially in the older population compared with younger adults. Recent data suggest a phenotype somewhat different from that of younger patients, also confirmed at the molecular level...
January 31, 2018: Drugs & Aging
https://www.readbyqxmd.com/read/29375131/a-modified-hla-a-0201-restricted-ctl-epitope-from-human-oncoprotein-hpebp4-induces-more-efficient-antitumor-responses
#18
Weihong Sun, Junyi Shi, Jian Wu, Junchu Zhang, Huabiao Chen, Yuanyuan Li, Shuxun Liu, Yanfeng Wu, Zhigang Tian, Xuetao Cao, Nan Li
We previously identified human phosphatidylethanolamine-binding protein 4 (hPEBP4) as an antiapoptotic protein with increased expression levels in breast, ovarian and prostate cancer cells, but low expression levels in normal tissues, which makes hPEBP4 an attractive target for immunotherapy. Here, we developed hPEBP4-derived immunogenic peptides for inducing antigen-specific cytotoxic T lymphocytes (CTLs) targeting breast cancer. A panel of hPEBP4-derived peptides predicted by peptide-MHC-binding algorithms was evaluated to characterize their HLA-A2...
January 29, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29373180/immunotherapy-an-evolving-approach-for-the-management-of-triple-negative-breast-cancer-converting-non-responders-to-responders
#19
REVIEW
Mai F Tolba, Hany A Omar
Immunotherapy comprises a promising new era in cancer therapy. Immune checkpoint inhibitors targeting either the programmed death (PD)-1 receptor or its ligand PD-L1 were first approved by the Food and Drug Administration (FDA) for the management of metastatic melanoma in 2011. The approval of this class is being extended to include other types of immunogenic tumors. Although breast cancer (BC) was first categorized as non-immunogenic tumor type, there are certain subsets of BC that showed a high level of tumor infiltrating lymphocytes (TILs)...
January 12, 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29371976/hdac-inhibition-potentiates-immunotherapy-in-triple-negative-breast-cancer
#20
Manuela Terranova-Barberio, Scott Thomas, Niwa Ali, Nela Pawlowska, Jeenah Park, Gregor Krings, Michael D Rosenblum, Alfredo Budillon, Pamela N Munster
Triple-negative breast cancer (TNBC) represents a more aggressive and difficult subtype of breast cancer where responses to chemotherapy occur, but toxicity is significant and resistance often follows. Immunotherapy has shown promising results in various types of cancer, including breast cancer. Here, we investigated a new combination strategy where histone deacetylase inhibitors (HDACi) are applied with immune checkpoint inhibitors to improve immunotherapy responses in TNBC. Testing different epigenetic modifiers, we focused on the mechanisms underlying HDACi as priming modulators of immunotherapy...
December 26, 2017: Oncotarget
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